Insulin resistance contributes to the pathogenesis of several disease states including obesity and type 2 diabetes mellitus . We have investigated the nature of the genetic factors that predipose to the development of insulin resistance. Previously, we have identified mutations in the insulin receptor gene in patients with several genetic syndromes associated with insulin resistance. More recently, we have been carrying out clinical investigation of patients with various forms of lipoatrophy, most of whom also have insulin resistant diabetes. In collaboration with Drs. A. Garg and A. Bowcock (Univ. Texas Southwestern), the gene for congenital generalized lipoatrophy has been mapped to chromosome 9q34. In addition, we have demonstrated that troglitazone therapy dramatically improves metabolic control in patients with lipoatrophic diabetes. In the course of follow-up, we will also determine whether troglitazone leads to an increase in body fat. Efforts are underway to develop new protocols to evaluate the potential benefit of newer therapeutic agents (including rosiglitazone, pioglitazone, and leptin). - insulin, insulin resistance, insulin receptor, tyrosine phosphorylation, diabetes, lipoatrophy, Dunnigan's syndrome, troglitazone - Human Subjects